The study concerns heritable diseases that affect the development and normal function of the skeleton. These include osteogenesis imperfecta, skeletal dysplasias, the various sub-type of Ehlers-Danlos syndrome, Marfan's syndrome, idiopathic scoliosis, and other less well known or previously undescribed heritable conditions. In a coordinated approach abnormalities are being sought in the molecular structure of collagen and other macromolecules by biochemical analysis and in the ultrastructure of the cells and extracellular matrix by electron microscopy. Collagen analyses include solubility, molecular typing, peptide mapping of component alpha-chains, crosslinking amino acids including newly identified non-reducible forms, content of hydroxylysine and hydroxylysine glycosides, and further compositional and biosynthetic properties of the individual alpha-chains dependent on the clinical condition and results of preliminary analyses. Aspects of proteoglycan and glycoprotein compositions will be examined. The diameter, weave and appearance of the collagen fibrils will be determined by electron microscopy, and also the distribution of proteoglycans in cartilage and other tissues. The ultrastructure of cells in the affected tissues will be studied, looking particularly for abnormalities in organelles that handle the export and resorption of matrix materials.